This invention relates to new naphthoquinone derivatives which exhibit antibiotic activity.
Many antibiotics used in medicine today are secondary metabolites produced by cultures of various species of fungi, or are semi-synthetic analogs derived from these metabolites. The ability of bacteria to develop resistance to antibiotics over a period of time requires that new sources and new compounds be continually discovered as replacements. In some cases bacterial resistance to a given antibiotic can by overcome be effecting a minor change in the molecular structure of the drug. However, the constant selective pressure of antibiotic exposure has led to the emergence of highly resistant strains of certain pathogens, such as Staphylococcus aureus. The broad spectrum resistance acquired by these bacterial strains greatly increases the hazard of such infections.
Fusarium solani is a soil-borne fungus which, when grown on certain media, elaborates a class of secondary metabolites known as naphthoquinones. Several of these compounds have been shown to have antibiotic activity against certain bacteria and fungi [H. Kern, Ann. Phytopathol. 10(3): 327-345 (1978)].
Studies relating soil aeration to disease state have focused on the effect of low oxygen stress on the plant, or on the plant-pathogen interaction, without considering the effect of such stress on the pathogen itself. F. solani responds to low pH and other imposed stresses by synthesizing a number of naphthoquinone derivatives [D. Parisot et al., J. Gen. Microbiol. 126: 443-457 (1981)]. These compounds, and others derived therefrom via oxidation, possess both phytotoxic and antibiotic properties [A. W. McColloch et al., Can. J. Chem. 60: 2943-2949 (1982)].
Minor structural differences profoundly influence the antimicrobial activities of these compounds. Some have little measurable inhibitory activity, while others of very similar structure are quite potent. Presence or lack of antimicrobial activity cannot be deduced simply by examination of the compound's structure.